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Turner Syndrome

Turner Syndrome. Synonyms and related keywords. 45 X Karyotype syndrome. Bonnevie-Ullrich syndrome. Gonadal dysgenesis. Monosomy X. History.  Henry Turner, 1938  Ford et al ., 1959. Frequency. 1 in 2,000 live-born female infants.

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Turner Syndrome

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  1. Turner Syndrome

  2. Synonyms and related keywords • 45 X Karyotype syndrome. • Bonnevie-Ullrich syndrome. • Gonadal dysgenesis. • Monosomy X.

  3. History Henry Turner, 1938 Ford et al., 1959

  4. Frequency • 1 in 2,000 live-born female infants. • 15% of spontaneous abortions have a 45,X0 Karyotype. In Sudan ? Race No racial or ethnic predilections.

  5. Genetic mechanisms 1. Absence of one copy of X chromosome.  Paternal loss in 62%  Maternal in 48% 2. Patient with Mosaic karyotype.  Ex. 46,XX/45,X 3. Structural rearrangement result in loss of Xp material. Ex. 46,iX(Xq) 4. Loss of the SHOX gene.  Variety of Turner syndrome.

  6. 45, X0 – Turner syndromes 99% of cases – aborted Total fetal hydrops 1 in 2,500 or 1 in 2,000 liveborn females. normal intelligence; may have 3D spatial problems or math problems. http://www.gfmer.ch/Genetic_diseases/Turner_syndrome/Turner.htm

  7. Web of skin Aorta Breast development Under- developed ovaries

  8. Phenotype 95% of adult with Turner syndrome exhibit short stature and infertility.

  9. Short stature

  10. Infertility 94% of patients are infertile Pregnancy has been achieved by: 1. Fresh embryo. 2. Frozen embryo transfer. Delivery by caesarean section is related to small pelvic outlet size.

  11. Patients may present with Ovarian failureprimary amenorrohoae.Undeveloped breast. 45,X[6]/46XX [80]

  12. Patients may present with Ambiguous genitalia

  13. Ambigious genitalia • Age • 7 month • Sex • Male • Diagnosis • Intersex • Examination • Big phallus, • Labia major. • Small L. minora. • Blind vagina. • Male urethra. • Ultrasound • NO uterus. • Testes could be identified. 46,X,del(X)(p11)[11].

  14. Low hairline.Shield-shaped chest.Narrow hip development. Patients may present with .

  15. Lymphedema • May be present at any age. • It is the cause of the webbed neck and low posterior hairline. • In infants, the combination of dysplastic or hypoplastic nails and lymphedema gives a characteristic sausage-like appearance to the fingers and toes.

  16. Patients may present with Lymphedema The toes have the characteristic sausage-like appearance

  17. Generalized lymphedema. Loose skin folds around the neck will form a webbed neck later in life

  18. Hyperconvex nails in Turner syndrome note U-shaped cross section

  19. Mortality and morbidity Mortality Is high due to: 1. Coarctation of the aorta. 2. Cardiovascular disease. 3. Obesity, associated diabetes and hypertension. 4. Osteoporosis. Life expectancy is reduced by 10 years. Morbidity Individuals with mitral or aortic valve disease require prophylaxis for sub acute bacterial endocarditis (SBE).

  20. Nephrology or urology • 35% of patients have renal anomalies. • Ultrasound evaluation at the diagnosis. • Yearly urine culture. • BUN, and creatinine. • Girls with horseshoe kidneys: • Have an increased risk of Wilms tumor. • Should have renal ultrasound examinations: • Every 5 months until the age of 8 years. • Every 6-12 months thereafter.

  21. Audiology Hearing assessment At birth At 1 year-age. Before entering school.  At adulthood.

  22. Cardiology A cardiologist should evaluate patients at diagnosis. 1. Risks of aortic root dilatation. 2. Risks of Aortic dissection. Complete cardiovascular evaluation For all patients prior to attempting assisted reproduction or conception.

  23. Endocrinology Supplement with: 1. Growth hormone. 2. Estrogens. 3. progestins. Attention should be paid to: 1. Growth and development, 2. Thyroid status 3. Osteoporosis. Patients on growth hormone should be seen every 3-4 months.

  24. Other • Gastrointestinal bleeding: • Hip dislocation: • Scoliosis in 10% of adolescent girls with Turner syndrome. • Thyroid: 10-30% develop hypothyroidism.

  25. Diagnosis Should be considered in Individuals with : • Primary or secondary amenorrhea. • Adult women with unexplained infertility • Unexplained short stature. Turner syndrome may be diagnosed prenatally by: 1. Amniocentesis. 2. Chorionic villous sampling.

  26. Diagnosis • The clinical suspicion • Cytogenetic analysis • 45,X. • 45, X/46, XX. • 46,XX,del(X)(P10). • FISH analysis. • Cytogenetic analysis of fibroblas • in case of normal karyotype 46,XX.

  27. FISH

  28. 45, X0 – Turner syndromes • Short Stature (approximately 4 feet 8 inches) –; loss of action SHOX gene on the X-chromosome. • No ovarian function or early loss of function (in late teens) • Coarctation of the aorta (narrow aorta) 10-15% • Kidney problem (Horseshoe kidney)  high blood pressure treated by growth hormone estrogen-progesterone treatment to maintain secondary sexual development Corrected surgically

  29. Medical Care In childhood Growth hormone therapy is standard to prevent short stature as an adult. Cecilia takes her daily growth hormone injection

  30. "My name is Regina and I’m 9 years old. I felt that taking my growth hormone injection was a bit difficult in the beginning, but I practiced with an orange and after a while I found out how to do it, and now it’s just a habit like brushing your teeth."

  31. Estrogen replacement • Therapy is required, but starting too early can compromise adult height. • Estrogen usually is started from age 12-15 years.

  32. Surgical Care Keloid formation Prophylaxis is required prior to and dental or surgical procedure in women with cardiac valve disease, to prevent subacute bacterial endocarditis. Turner syndrome individuals exhibits high risk of keloid formation. Subacute bacterial endocarditis

  33. Surgical Care Before After surgery

  34. Diet • Ovarian failure are risk factors for osteoporosis thus adequate daily intake of calcium (1.0-1.5 g) and vitamin D (at least 400 IU) should consider. • Patients with short stature require fewer calories than those of normal height.

  35. Genetics counseling • Turner syndrome is not an inherited disorder, and the recurrence risk is low. • Due to infertility, it is rarely passed to offspring. • Consultation with a geneticist 1. Suspected mosaicism for all, or part 2. Virilization with part of Y chromosome.

  36. Prognosis • Overall prognosis is good. • Even with growth hormone therapy, most individuals will be shorter than average. • Turner syndrome is not a cause of mental retardation. Life expectancy is slightly shorter. Almost all individuals will be infertile, but pregnancy with donor embryos is possible.

  37. Medical and legal pitfalls • Yearly follow-up TSH tests will help avoid unrecognized hypothyroidism, which can interfere with growth. • Osteoporosis and aortic arch dissection are known complications in adulthood.

  38. Dosage Compensation • Shouldn’t XX females produce twice the amount of X-linked gene products (proteins) as XY males? • No, because XX females “compensate” by inactivating one of their X chromosomes to make a single “dosage” of X-linked genes.

  39. Barr Bodies are inactivated X chromosomes in Females Normal female, Klinefelter male Normal male, Turner female 0 1 2 3 # Barr bodies= N-1 rule

  40. Inconsistencies between syndromes and X inactivation • If normal XX female has one X inactivated, • why is a X Turner female not normal? • Similarly, if XXY male has one X • inactivated, why does he have Klinefelter • syndrome? Perhaps not complete inactivation or inactivation does not happen immediately, Then some overexpression of X-linked genes

  41. The Lyon Hypothesis of X Inactivation • Proposed by Mary Lyon and Liane Russell (1961) • Which X is inactivated? Inactivation of X chromosome occurs randomly in somatic cells during embryogenesis • Progeny of cells all have same inactivated X chromosome as original, creating mosaic individual

  42. Lyon-Hypothesis: X-inactivation A precursor cell to all coat color cells Random inactivation early in dev. **Also in calico cats

  43. Inactive Xs condense to form Barr bodies during development Inactivation is random during development Color pattern seen in female calico cats due to random X chromosome inactivation Barr bodies in female cells X chromosome inactivation • X chromosome has many more genes than the Y chromosome • Females have 2 Xs • One X must be inactivated to preserve gene dosage

  44. Mosaicism Reveals the Random Inactivation of one X chromosome Anhidroticectodermal dysplasia in a heterozygous woman Regions where sweat glands are absent.

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